Olivocochlear (OC) efferent suppression of auditory-nerve responses compris
es a fast effect lasting tens of milliseconds and a slow effect building an
d decaying over tens of seconds. Both fast and slow effects are mediated by
activation of the same alpha 9 nicotinic receptor. We have hypothesized th
at fast effects are generated at the OC synapse, but that slow effects refl
ect activation of calcium-activated potassium (K-Ca) channels by calcium re
lease from the subsurface cisternae on the basolateral wall of the hair cel
ls. We measured in vivo effects of apamin, a blocker of small-conductance (
SK) K-Ca channels, and charybdotoxin, a blocker of large-conductance K-Ca c
hannels, perfused through scala tympani, on fast and slow effects evoked by
electrical stimulation of the OC bundle in anesthetized guinea pigs. Apami
n selectively and reversibly reduced slow-effect amplitude without altering
fast effects or baseline amplitude of the auditory-nerve response, but onl
y when perfused at concentrations of 100 muM. In contrast, the effects of c
harybdotoxin were noted at 30 nM, but were not specific, reducing both affe
rent and efferent responses. The very high concentrations of apamin needed
to block efferent effects contrasts with the high sensitivity of isolated h
air cells to apamin's block of acetylcholine's effects. The results suggest
that in vivo fast OC effects are dominated by a conductance that is not ap
amin sensitive.